DESCRIPTION (Applicant's Description): The integrin family of cell surface receptors mediate interactions with extracellular matrix proteins and between adjacent cells. These interactions play an important role in normal growth and development, the regulation of programmed cell death and tumor cell growth and metastasis. Recent evidence indicates that integrins can activate signal transduction pathways and regulate gene expression. This research proposal is aimed at studying integrin-dependent activation of signaling in fibroblast cells. Three aims are proposed. First, the investigators will identify which signal transduction pathways are activated upon integrin engagement. They will determine the signaling intermediaries utilized by integrin and mitogen activation of a particular pathway. Second, they will study the role of focal adhesion kinase and associated proteins in activating these pathways. They will characterize the functional interactions between proteins involved in both integrin and mitogen signaling. Third, they will attempt to determine how integrin-mediated signaling regulates programmed cell death, or apoptosis. They will attempt to modulate the activity of proteins involved in integrin signaling and determine the effects on apoptosis. Understanding integrin signaling in normal cells will allow future comparison of the same pathways in malignant cells, potentially revealing new insights into the transformed phenotype.